Effects of endothelin receptor blockade and COX inhibition on intestinal I/R injury in a rat model: Experimental research

Bercis Imge Ucar; Acelya Erikci; Kemal Kosemehmetoglu; Ceren Ozkul; Alper Bektas Iskit; Gulberk Ucar; Sezgin Zeren

doi:10.1016/j.ijsu.2020.08.061

Effects of endothelin receptor blockade and COX inhibition on intestinal I/R injury in a rat model: Experimental research

Int J Surg. 2020 Nov:83:89-97. doi: 10.1016/j.ijsu.2020.08.061. Epub 2020 Sep 16.

Authors

Bercis Imge Ucar¹, Acelya Erikci², Kemal Kosemehmetoglu³, Ceren Ozkul⁴, Alper Bektas Iskit⁵, Gulberk Ucar², Sezgin Zeren⁶

Affiliations

¹ Department of General Surgery, Faculty of Medicine, Kutahya Health Sciences University, Kutahya, Turkey. Electronic address: bercis.imge@gmail.com.
² Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
³ Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
⁴ Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
⁵ Department of Medical Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
⁶ Department of General Surgery, Faculty of Medicine, Kutahya Health Sciences University, Kutahya, Turkey.

PMID: 32947061
DOI: 10.1016/j.ijsu.2020.08.061

Abstract

Background: Intestinal ischemia is a highly morbid and mortal condition with no specific treatment. The present study aimed to investigate the effects of cyclooxygenase (COX) inhibition synchronized with nitric oxide (NO) release and endothelin (ET) receptor blockade on oxidative stress, inflammation, vasoconstriction, and bacterial translocation which occur during ischemia-reperfusion (I/R) injury in in-vivo rat intestinal I/R model.

Materials and methods: 36 male Wistar rats were randomly divided into six groups (n = 6). Superior mesenteric artery blood flow (SMABF) was recorded; SMA was occluded for 30 min; SMABF was re-recorded at the beginning of the reperfusion phase. Rats were sacrificed after the reperfusion period of 60 min. Blood and tissue samples were obtained. Acetylsalicylic acid (ASA), NO-ASA, flurbiprofen (FLUR), and Tezosentan (TS) were administered 15 min after ischemia. Histopathological examination, bacterial translocation, and biochemical analysis were performed in plasma and tissue samples.

Results: SMABF difference, mean Chiu's score and bacterial translocation were increased in the I/R group and decreased in the treatment groups. Plasma LDH, transaminases, intestinal fatty acid-binding protein (I-FABP), TNF-α, ICAM-1, interferon-gamma (IFN-Ɣ) and proinflammatory cytokine panel; tissue lipid peroxidation, MPO, xanthine oxidase (XO), NO, NF-kB levels and the expression of TNF-α were significantly elevated in the I/R group and markedly decreased in the treatment groups. The tissue antioxidant status was decreased in the I/R group and increased in the treatment groups.

Conclusion: It is suggested that NO-ASA, TS, and FLUR can be introduced as promising therapeutics to improve intestinal I/R injury.

Institutional protocol no: 2018-29-05 (Animal Experimentations Ethics Committee, Hacettepe University).

Keywords: Cyclooxygenase inhibition; Endothelin receptor blockers; Intestinal ischemia reperfusion injury; Nitric oxide; Rat.

MeSH terms

Animals
Cyclooxygenase Inhibitors / therapeutic use*
Disease Models, Animal
Endothelin Receptor Antagonists / therapeutic use*
Intestines / blood supply
Male
Mesenteric Artery, Superior / physiopathology
Mesenteric Ischemia / drug therapy*
Rats
Rats, Wistar
Reperfusion Injury / metabolism
Reperfusion Injury / prevention & control*
Tumor Necrosis Factor-alpha / blood

Substances

Cyclooxygenase Inhibitors
Endothelin Receptor Antagonists
Tumor Necrosis Factor-alpha